title: Down-regulation of microglial activity attenuates axotomized nigral dopaminergic neuronal cell loss.
abstract: BACKGROUND
  There is growing evidence that inflammatory processes of activated microglia could play an important role in the progression of nerve cell damage in neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease which harbor features of chronic microglial activation, though the precise mechanism is unknown. In this study, we presented in vivo and ex vivo experimental evidences indicating that activated microglia could exacerbate the survival of axotomized dopaminergic neurons and that appropriate inactivation of microglia could be neuroprotective.
  
  
  RESULTS
  The transection of medial forebrain bundle (MFB) of a rat induced loss of dopaminergic neurons in a time-dependent manner and accompanied with microglial activation. Along with microglial activation, production of reactive oxygen species (ROS) was upregulated and TH/OX6/hydroethidine triple-immunofluorescence showed that the microglia mainly produced ROS. When the activated microglial cells that were isolated from the substantia nigra of the MFB axotomized animal, were transplanted into the substantia nigra of which MFB had been transected at 7 days ago, the survival rate of axotomized dopaminergic neurons was significantly reduced as compared with sham control. Meanwhile, when the microglial activation was attenuated by administration of tuftsin fragment 1-3 (microglia inhibitory factor) into the lateral ventricle using mini-osmotic pump, the survival rate of axotomized dopaminergic neurons was increased.
  
  
  CONCLUSIONS
  The present study suggests that activated microglia could actively produce and secrete unfavorable toxic substances, such as ROS, which could accelerate dopaminergic neuronal cell loss. So, well-controlled blockade of microglial activation might be neuroprotective in some neuropathological conditions.
authors.affiliation: Department of Anatomy and Neuroscience, Eulji University School of Medicine, 143-5, Yongdu-dong, 301-832 Jung-gu, Daejeon, Republic of KoreaKorea. jbl0719@naver.com.
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Song
authors.forename: Ha-Nul
authors.initials: HN
authors.lastname: Yu
authors.forename: Chae-Ri
authors.initials: CR
authors.lastname: Park
authors.forename: Jin-Sook
authors.initials: JS
authors.lastname: Lee
authors.forename: Ji-Yong
authors.initials: JY
authors.lastname: Lee
authors.forename: Byung-Gu
authors.initials: BG
authors.lastname: Park
authors.forename: Ran-Sook
authors.initials: RS
authors.lastname: Woo
authors.forename: Jung-Tae
authors.initials: JT
authors.lastname: Han
authors.forename: Byung-Pil
authors.initials: BP
authors.lastname: Cho
authors.forename: Tai-Kyoung
authors.initials: TK
authors.lastname: Baik
mesh_terms: D000818:Animals; D019771:Axotomy; D015153:Blotting, Western; D059290:Dopaminergic Neurons / Q000473:pathology*; D015536:Down-Regulation; D007150:Immunohistochemistry; D008297:Male; D008474:Medial Forebrain Bundle / Q000293:injuries; D017628:Microglia / Q000378:metabolism*; D009410:Nerve Degeneration / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013378:Substantia Nigra / Q000473:pathology
chemical_list: D017382:Reactive Oxygen Species